Efficacy of regorafenib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND: Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma (HCC), but its comparative efficacy remains under evaluation. AIM: other second-line therapies in advanced HCC. METHODS: This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. A comprehensive search of PubMed, EMBASE, Web of Science, and the Cochrane Library was performed on June 6, 2025. Studies were included if they reported at least one relevant clinical outcome: Overall survival, progression-free survival, objective response rate, or disease control rate. Data was extracted independently by two reviewers. Quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies. Pooled effect estimates were calculated using random- or fixed-effects models depending on the degree of heterogeneity. Sensitivity analyses and Egger's test were performed to evaluate the robustness of the results and potential publication bias. RESULTS: < 0.05], but no significant benefit was observed for progression-free survival (weighted mean difference = 1.04; 95%CI: -1.27 to 3.36). The pooled objective response rate showed no overall difference, though regorafenib was inferior to nivolumab in subgroup analysis (odds ratio = 0.34; 95%CI: 0.20-0.58). Disease control rate did not differ significantly. No publication bias was detected. CONCLUSION: Regorafenib offers a survival advantage in advanced HCC but does not significantly improve tumor response rates compared to alternative therapies.